Clinico-genomic analysis of Lynch-like syndrome

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07187
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Tokyo Metropolitan Hospital Organization Tokyo Metropolitan Komagome Hospital
• Principal Investigator: Yamaguchi Tatsuro 地方独立行政法人東京都立病院機構東京都立駒込病院(臨床研究室), 遺伝子診療科, 部長 (10538482)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Lynch-like症候群 / 遺伝性腫瘍 / Lynch症候群 / MSI / マイクロサテライト不安定性 / 大腸癌

Outline of Final Research Achievements

In total, 2634 consecutive patients with CRC were enrolled between 2008 and 2019.
UTS of the cohort found 146 patients with MSI CRC (5.5%). Of these, excluding sporadic MSI CRC, 30 (1.1%) had a diagnosis of LS, and 19 (0.7%) had no germline pathogenic variants of the MMR gene. The CRC type in the latter group was identified as LLS. LLS occurred significantly more often in young patients, was left-sided, involved a KRAS variant and BRAF wild-type, and had a higher concordance rate with the Revised Bethesda Guidelines than sporadic MSI CRC. No significant differences were observed in terms of the clinicopathological factors between LLS and LS-associated MSI CRC; however, LLS had a lower frequency of LS-related neoplasms compared with LS.
In conclusion, distinguishing clinically between LS and LLS was challenging, but the incidence of neoplasms was higher in LS than in LLS, suggesting the need for different screening and surveillance methods for the two subtypes.

Free Research Field

遺伝性腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究は、Lynch症候群および散発性MSI大腸癌と比較し、Lynch-like症候群の臨床的特徴を明らかにした。その結果、Lynch-like症候群の患者はLynch症候群や散発性MSI大腸癌とは異なるサーベイランス方法が必要であることが明らかとなった。
現在、Lynch症候群診断のための遺伝学的検査は保険適用外であるが、Lynch-like症候群とLynch症候群の鑑別は遺伝学的検査によってのみ行われる。したがって、Lynch症候群診断のための遺伝学的検査は診断・サーベイランスの観点から必要であると考えられた。